a study to evaluate the safety and therapeutic activity of gi-102 as a single agent and in combination with conventional anti-cancer drugs, pembrolizumab or trastuzumab deruxtecan(t-dxd) in patients with advanced solid tumors (keynote-g08)

Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Soft Tissue Sarcoma (STS); Platinum-resistant Ovarian Cancer (PROC); Hepatocellular Carcinoma (HCC); Colorectal Cancer (CRC); HER2 Negative Breast Cancer; Cutaneous Melanoma; Renal Cell Carcinoma (RCC)

Summary: the purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of gi-102 as a single agent and in combination with conventional anti-cancer drugs, pembrolizumab or trastuzumab deruxtecan(t-dxd) over a range of advanced and/or metastatic solid tumors.

this is a phase 1/2, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, and anti-tumor effect of gi-102 as a single agent and in combination with conventional anti-cancer drugs, pembrolizumab or trastuzumab deruxtecan(t-dxd) over a range of advanced and/or metastatic solid tumors. this study is adaptive in nature. the study is composed of four parts: * part a: dose escalation and optimization phase of gi-102 intravenous (iv) monotherapy * part a dose escalation phase * part a dose optimization phase: dose optimization cohorts in patients with 2l+, cpi-refractory metastatic melanoma * part b: dose escalation and expansion phase of gi-102 subcutaneous (sc) monotherapy * part c: indication specific cohorts of gi-102 iv in combination with conventional anti-cancer drugs or trastuzumab deruxtecan (t-dxd) * part d: indication specific cohorts of gi-102 iv in combination with pembrolizumab gi-102 is a novel bi-specific fc fusion protein containing the cd80 ectodomain as an n-terminal moiety and an interleukin (il)-2 variant as a c-terminal moiety configurated via a human immunoglobulin g4 (igg4) fc. gi-102 has unique characteristics by having bispecificity to cd80 and il2rβγ. the cd80 portion is responsible for targeting tumor/immune cells while blocking ctla-4 expressed on the treg cells. the il-2v of gi-102 is designed to abolish il-2rα affinity and therefore minimize the effect on treg while it has very outstanding effect on nk and cd8 t cell proliferation and activity through il-2rbr affinity.

Eligibility criteria:
key inclusion criteria: * males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening. * has adequate organ and marrow function as defined in protocol. * measurable disease as per recist v1.1. * ecog performance status 0-1. * adverse events related to any prior chemotherapy, radiotherapy, immunotherapy, other prior systemic anti-cancer therapy, or surgery must have resolved to grade ≤1, except alopecia and grade 2 peripheral neuropathy. * hiv infected patients must be on anti-retroviral therapy (art) and have a well-controlled hiv infection/disease as defined in protocol. key exclusion criteria: * has known active cns metastases and/or carcinomatous meningitis. * an active second malignancy. * has active or a known history of hepatitis b or known active hepatitis c virus infection. * has active tuberculosis or has a known history of active tuberculosis. * active or uncontrolled infections, or severe infection within 4 weeks before study treatment administration. * history of chronic liver disease or evidence of hepatic cirrhosis, except patients with liver metastasis. * has an active autoimmune disease that has required systemic treatment in past 2 years. * previous immunotherapies related to mode of action of gi-102. * has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive medications within 2 weeks prior to cycle 1 day 1. * administration of prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment. * radiotherapy within the last 2 weeks before start of study treatment administration, with exception of limited field palliative radiotherapy. * administration of a live, attenuated vaccine within 4 weeks before cycle 1 day 1. * known hypersensitivity to any of the components of the drug products and/or excipients of gi-102. other protocol defined inclusion exclusion criteria may apply

Keywords: gi-102 cd80-igg4 fc-il2 variant immunotherapy il-2 interleukin-2 bispecific protein immunocytokine cd80 ctla-4 pembrolizumab t-dxd trastuzumab deruxtecan doxorubicin paclitaxel bevacizumab eribulin